tbuckley/cabot-search huggingface dataset:
Patient-Specific Targeting of the T-Cell Receptor Variable Region as a Therapeutic Strategy in Clonal T-Cell Diseases
Authors: Olivia M. Lucero, Ji-Ann Lee, Jenna Bowman, Kara Johnson, Gopal Sapparapu, John K. Thomas, Guang Fan, Bill H. Chang, Karina Thiel-Klare, Christopher A. Eide, Craig Okada, Mike Palazzolo, Evan Lind, Yoko Kosaka, Brian J. Druker, Nicholas Lydon, Peter M. Bowers
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Targeted therapeutics are a goal of medicine. Methods for targeting T-cell lymphoma lack specificity for the malignant cell, leading to elimination of healthy cells. The T-cell receptor (TCR) is designed for antigen recognition. T-cell malignancies expand from a single clone that expresses one of 48 TCR variable beta (Vβ) genes, providing a distinct therapeutic target. We hypothesized that a mAb that is exclusive to a specific Vβ would eliminate the malignant clone while having minimal effects on healthy T cells. Experimental Design: We identified a patient with large granular T-cell leukemia and sequenced his circulating T-cell population, 95% of which expressed Vβ13.3. We developed a panel of anti-Vβ13.3 antibodies to test for binding and elimination of the malignant T-cell clone. Results: Therapeutic antibody candidates bound the malignant clone with high affinity. Antibodies killed engineered cell lines expressing the patient TCR Vβ13.3 by antibody-dependent cellular cytotoxicity and TCR-mediated activation-induced cell death, and exhibited specific killing of patient malignant T cells in combination with exogenous natural killer cells. EL4 cells expressing the patient's TCR Vβ13.3 were also killed by antibody administration in an in vivo murine model. Conclusions: This approach serves as an outline for development of therapeutics that can treat clonal T-cell–based malignancies and potentially other T-cell–mediated diseases. See related commentary by Varma and Diefenbach, p. 4024
Reply: ELF in the risk stratification of NAFLD—Are the ELF thresholds suggested by the AASLD guidelines appropriate?
Authors: Mary E. Rinella, Norah Terrault, Brent Neuschwander-Tetri, Rohit Loomba, Manal Abdelmalek
Journal: Hepatology (2023)

1The University of Chicago 2University of Southern California, AASLD President Correspondence Mary E. Rinella, MD, University of Chicago Biological Sciences Division. Email: [email protected]
Clinical epidemiology and case fatality due to antimicrobial resistance in Germany: a systematic review and meta-analysis, 1 January 2010 to 31 December 2021
Authors: Maria Rödenbeck, Olaniyi Ayobami, Tim Eckmanns, Mathias W Pletz, Jutta Bleidorn, Robby Markwart
Journal: Eurosurveillance (2023)

Background Antimicrobial resistance (AMR) is of public health concern worldwide. Aim We aimed to summarise the German AMR situation for clinicians and microbiologists. Methods We conducted a systematic review and meta-analysis of 60 published studies and data from the German Antibiotic-Resistance-Surveillance (ARS). Primary outcomes were AMR proportions in bacterial isolates from infected patients in Germany (2016–2021) and the case fatality rates (2010–2021). Random and fixed (common) effect models were used to calculate pooled proportions and pooled case fatality odds ratios, respectively. Results The pooled proportion of meticillin resistance in Staphylococcus aureus infections (MRSA) was 7.9% with a declining trend between 2014 and 2020 (odds ratio (OR) = 0.89; 95% CI: 0.886–0.891; p &lt; 0.0001), while vancomycin resistance in Enterococcus faecium (VRE) bloodstream infections increased (OR = 1.18; (95% CI: 1.16–1.21); p &lt; 0.0001) with a pooled proportion of 34.9%. Case fatality rates for MRSA and VRE were higher than for their susceptible strains (OR = 2.29; 95% CI: 1.91–2.75 and 1.69; 95% CI: 1.22–2.33, respectively). Carbapenem resistance in Gram-negative pathogens ( Klebsiella pneumoniae , Acinetobacter baumannii , Enterobacter spp. and Escherichia coli ) was low to moderate (&lt; 9%), but resistance against third-generation cephalosporins and fluoroquinolones was moderate to high (5–25%). Pseudomonas aeruginosa exhibited high resistance against carbapenems (17.0%; 95% CI: 11.9–22.8), third-generation cephalosporins (10.1%; 95% CI: 6.6–14.2) and fluoroquinolones (24.9%; 95% CI: 19.3–30.9). Statistical heterogeneity was high (I 2 &gt; 70%) across studies reporting resistance proportions. Conclusion Continuous efforts in AMR surveillance and infection prevention and control as well as antibiotic stewardship are needed to limit the spread of AMR in Germany.
Trinh BQ, Ummarino S, Zhang Y, et al. Myeloid lncRNA <i>LOUP</i> mediates opposing regulatory effects of RUNX1 and RUNX1-ETO in t(8;21) AML. <i>Blood.</i> 2021;138(15):1331-1344.
Authors: Paolo Pandolfi, Daniel Tenen, Bon Trinh, Simone Ummarino, Yanzhou Zhang, Alexander Ebralidze, Mahmoud Bassal, Tuan Nguyen, Gerwin Heller, Rory Coffey, Danielle Tenen, Emiel Van Der Kouwe, Emiliano Fabiani, Carmelo Gurnari, Chan-Shuo Wu, Vladimir Angarica, Henry Yang, Sisi Chen, Hong Zhang, Abby Thurm, Francisco Marchi, Elena Levantini, Philipp Staber, Pu Zhang, Maria Voso, Pier Pandolfi, Susumu Kobayashi, Li Chai, Annalisa Ruscio, Daniel Tenen
Journal: Blood (2023)
Risk of Syndrome-Associated Cancers Among First-Degree Relatives of Patients With Pancreatic Ductal Adenocarcinoma With Pathogenic or Likely Pathogenic Germline Variants
Authors: Xuan Chen, Margaret A. Meyer, Jennifer L. Kemppainen, Masayasu Horibe, Shruti Chandra, Shounak Majumder, Gloria M. Petersen, Kari G. Rabe
Journal: JAMA Oncology (2023)

Increased cancer risk in first-degree relatives of probands with pancreatic ductal adenocarcinoma (PDAC probands) who carry pathogenic or likely pathogenic germline variants (PGVs) in cancer syndrome-associated genes encourages cascade genetic testing. To date, unbiased risk estimates for the development of cancers on a gene-specific basis have not been assessed.
Children and adolescents with attention deficit hyperactivity disorder and autism spectrum disorder share distinct microbiota compositions
Authors: Caspar Bundgaard-Nielsen, Marlene Briciet Lauritsen, Julie Kristine Knudsen, Louise Søndergaard Rold, Margit Hørup Larsen, Peter Hindersson, Annemarie Brusen Villadsen, Peter D. C. Leutscher, Søren Hagstrøm, Mette Nyegaard, Suzette Sørensen
Journal: Gut Microbes (2023)

An association has been suggested between altered gut microbiota, and attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), respectively. Thus, we analyzed the gut microbiota composition in children and adolescents with or without these disorders and evaluated the systemic effects of these bacteria. We recruited study participants diagnosed with ADHD, ASD, and comorbid ADHD/ASD, while the control groups consisted both of siblings and non-related children. The gut microbiota was analyzed by 16S rRNA gene sequencing of the V4 region, while the concentration of lipopolysaccharide-binding protein (LBP), cytokines, and other signaling molecules were measured in plasma. Importantly the gut microbiota compositions of cases with ADHD and ASD were highly similar for both alpha- and beta-diversity while differing from that of non-related controls. Furthermore, a subset of ADHD and ASD cases had an increased LBP concentration compared to non-affected children, which was positively correlated with interleukin (IL)-8, 12, and 13. These observations indicate disruption of the intestinal barrier and immune dysregulation among the subset of children with ADHD or ASD.
External Control Arms and Data Analysis Methods in Nonrandomized Trial of Patients With Glioblastoma—Reply
Authors: Linda M. Liau, Keyoumars Ashkan, Marnix L. Bosch
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Shorter Door-to-Needle Times Are Associated With Better Outcomes After Intravenous Thrombolytic Therapy and Endovascular Thrombectomy for Acute Ischemic Stroke
Authors: Shumei Man, Nicole Solomon, Brian Mac Grory, Brooke Alhanti, Ken Uchino, Jeffrey L. Saver, Eric E. Smith, Ying Xian, Deepak L. Bhatt, Lee H. Schwamm, Muhammad Shazam Hussain, Gregg C. Fonarow
Journal: Circulation (2023)

Background: Existing data and clinical trials could not determine whether faster intravenous thrombolytic therapy (IVT) translates into better long-term functional outcomes after acute ischemic stroke among those treated with endovascular thrombectomy (EVT). Patient-level national data can provide the required large population to study the associations between earlier IVT, versus later, with longitudinal functional outcomes and mortality in patients receiving IVT+EVT combined treatment. Methods: This cohort study included older US patients (age ≥65 years) who received IVT within 4.5 hours or EVT within 7 hours after acute ischemic stroke using the linked 2015 to 2018 Get With The Guidelines–Stroke and Medicare database (38 913 treated with IVT only and 3946 with IVT+EVT). Primary outcome was home time, a patient-prioritized functional outcome. Secondary outcomes included all-cause mortality in 1 year. Multivariate logistic regression and Cox proportional hazards models were used to evaluate the associations between door-to-needle (DTN) times and outcomes. Results: Among patients treated with IVT+EVT, after adjusting for patient and hospital factors, including onset-to-EVT times, each 15-minute increase in DTN times for IVT was associated with significantly higher odds of zero home time in a year (never discharged to home) (adjusted odds ratio, 1.12 [95% CI, 1.06–1.19]), less home time among those discharged to home (adjusted odds ratio, 0.93 per 1% of 365 days [95% CI, 0.89–0.98]), and higher all-cause mortality (adjusted hazard ratio, 1.07 [95% CI, 1.02–1.11]). These associations were also statistically significant among patients treated with IVT but at a modest degree (adjusted odds ratio, 1.04 for zero home time, 0.96 per 1% home time for those discharged to home, and adjusted hazard ratio 1.03 for mortality). In the secondary analysis where the IVT+EVT group was compared with 3704 patients treated with EVT only, shorter DTN times (≤60, 45, and 30 minutes) achieved incrementally more home time in a year, and more modified Rankin Scale 0 to 2 at discharge (22.3%, 23.4%, and 25.0%, respectively) versus EVT only (16.4%, P &lt;0.001 for each). The benefit dissipated with DTN&gt;60 minutes. Conclusions: Among older patients with stroke treated with either IVT only or IVT+EVT, shorter DTN times are associated with better long-term functional outcomes and lower mortality. These findings support further efforts to accelerate thrombolytic administration in all eligible patients, including EVT candidates.
Different inflammatory features of asthma according to gut microbiome enterotype
Authors: Kyoung‐Hee Sohn, Sungmi Choi, Jae‐Woo Jung, Jeong‐Hee Choi, Sang‐Heon Cho, Hana Yi, Hye‐Ryun Kang
Journal: Allergy (2023)

Appendix S1 Figure S1 Figure S2 Figure S3 Figure S4 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Cost-Related Medication Nonadherence and Desire for Medication Cost Information Among Adults Aged 65 Years and Older in the US in 2022
Authors: Stacie B. Dusetzina, Robert J. Besaw, Christine C. Whitmore, T. Joseph Mattingly, Anna D. Sinaiko, Nancy L. Keating, Jordan Everson
Journal: JAMA Network Open (2023)

Importance Rising prescription drug costs and increasing prices for consumer goods may increase cost-related medication nonadherence. Cost-conscious prescribing can be supported by real-time benefit tools, but patient views on real-time benefit tool use and their potential benefits and harms are largely unexplored. Objective To assess older adults’ cost-related medication nonadherence, cost-coping strategies, and views on the use of real-time benefit tools in clinical practice. Design, Setting, and Participants A weighted, nationally representative survey of adults aged 65 years and older administered via the internet and telephone from June 2022 to September 2022. Main Outcomes and Measures Cost-related medication nonadherence; cost coping strategies; desire for cost conversations; potential benefits and harms from real-time benefit tool use. Results Among 2005 respondents, most were female (54.7%) and partnered (59.7%); 40.4% were 75 years or older. Cost-related medication nonadherence was reported by 20.2% of participants. Some respondents used extreme forms of cost-coping, including foregoing basic needs (8.5%) or going into debt (4.8%) to afford medications. Of respondents, 89.0% reported being comfortable or neutral about being screened before a physician's visit for wanting to have medication cost conversations and 89.5% indicated a desire for their physician to use a real-time benefit tool. Respondents expressed concern if prices were inaccurate, with 49.9% of those with cost-related nonadherence and 39.3% of those without reporting they would be extremely upset if their actual medication price was more than what their physician estimated with a real-time benefit tool. If the actual price was much more than the estimated real-time benefit tool price, nearly 80% of respondents with cost-related nonadherence reported that it would affect their decision to start or keep taking a medication. Furthermore, 54.2% of those with any cost-related nonadherence and 30% of those without reported they would be moderately or extremely upset if their physicians used a medication price tool but chose not to discuss prices with them. Conclusions and Relevance In 2022, approximately 1 in 5 older adults reported cost-related nonadherence. Real-time benefit tools may support medication cost conversations and cost-conscious prescribing, and patients are enthusiastic about their use. However, if disclosed prices are inaccurate, there is potential for harm through loss of confidence in the physician and nonadherence to prescribed medications.
Safety and Effectiveness of Pulsed Field Ablation to Treat Atrial Fibrillation: One-Year Outcomes From the MANIFEST-PF Registry
Authors: Mohit K. Turagam, Petr Neuzil, Boris Schmidt, Tobias Reichlin, Kars Neven, Andreas Metzner, Jim Hansen, Yuri Blaauw, Philippe Maury, Thomas Arentz, Philipp Sommer, Ante Anic, Frédéric Anselme, Serge Boveda, Tom Deneke, Stephan Willems, Pepijn van der Voort, Roland Tilz, Moritoshi Funasako, Daniel Scherr, Reza Wakili, Daniel Steven, Josef Kautzner, Johan Vijgen, Pierre Jais, Jan Petru, Julian Chun, Laurent Roten, Anna Füting, Marc D. Lemoine, Martin Ruwald, Bart A Mulder, Anne Rollin, Heiko Lehrmann, Thomas Fink, Zrinka Jurisic, Corentin Chaumont, Raquel Adeliño, Karin Nentwich, Melanie Gunawardene, Alexandre Ouss, Christian-Hendrik Heeger, Martin Manninger, Jan-Eric Bohnen, Arian Sultan, Petr Peichl, Pieter Koopman, Nicolas Derval, Thomas Kueffer, Gilbert Rahe, Vivek Y. Reddy
Journal: Circulation (2023)

Pulsed field ablation is a novel nonthermal cardiac ablation modality using ultra-rapid electrical pulses to cause cell death by a mechanism of irreversible electroporation. Unlike the traditional ablation energy sources, pulsed field ablation has demonstrated significant preferentiality to myocardial tissue ablation, and thus avoids certain thermally mediated complications. However, its safety and effectiveness remain unknown in usual clinical care.MANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-Approval Clinical Use of Pulsed Field Ablation) is a retrospective, multinational, patient-level registry wherein patients at each center were prospectively included in their respective center registries. The registry included all patients undergoing postapproval treatment with a multielectrode 5-spline pulsed field ablation catheter to treat atrial fibrillation (AF) between March 1, 2021, and May 30, 2022. The primary effectiveness outcome was freedom from clinical documented atrial arrhythmia (AF/atrial flutter/atrial tachycardia) of ≥30 seconds on the basis of electrocardiographic data after a 3-month blanking period (on or off antiarrhythmic drugs). Safety outcomes included the composite of acute (<7 days postprocedure) and latent (>7 days) major adverse events.At 24 European centers (77 operators) pulsed field ablation was performed in 1568 patients with AF: age 64.5±11.5 years, female 35%, paroxysmal/persistent AF 65%/32%, CHA2DS2-VASc 2.2±1.6, median left ventricular ejection fraction 60%, and left atrial diameter 42 mm. Pulmonary vein isolation was achieved in 99.2% of patients. After a median (interquartile range) follow-up of 367 (289-421) days, the 1-year Kaplan-Meier estimate for freedom from atrial arrhythmia was 78.1% (95% CI, 76.0%-80.0%); clinical effectiveness was more common in patients with paroxysmal AF versus persistent AF (81.6% versus 71.5%; P=0.001). Acute major adverse events occurred in 1.9% of patients.In this large observational registry of the postapproval clinical use of pulsed field technology to treat AF, catheter ablation using pulsed field energy was clinically effective in 78% of patients with AF.
External Control Arms and Data Analysis Methods in Nonrandomized Trial of Patients With Glioblastoma
Authors: Jacob J. Mandel, John F. de Groot
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Letter to the Editor: Updated guidance on NAFLD screening
Authors: María Teresa Arias-Loste, Javier Crespo, Paula Iruzubieta
Journal: Hepatology (2023)

1Hospital Universitario Marques de Valdecilla, Gastroenterology and Hepatology; Instituto de Investigación Marqués de Valdecilla 2Hospital Universitario Marques de Valdecilla, Gastroenterology 3Marqués de Valdecilla University Hospital, Gastroenterology and Hepatology Uni Correspondence María T. Arias-Loste, Hospital Universitario Marques de Valdecilla, Gastroenterology and Hepatology; Instituto de Investigación Marqués de Valdecilla. Email: [email protected]
Vaccine Effectiveness of JYNNEOS against Mpox Disease in the United States
Authors: Nicholas P. Deputy, Joseph Deckert, Anna N. Chard, Neil Sandberg, Danielle L. Moulia, Eric Barkley, Alexandra F. Dalton, Cory Sweet, Amanda C. Cohn, David R. Little, Adam L. Cohen, Danessa Sandmann, Daniel C. Payne, Jacqueline L. Gerhart, Leora R. Feldstein
Journal: New England Journal of Medicine (2023)

In the United States, more than 30,000 cases of mpox (formerly known as monkeypox) had occurred as of March 1, 2023, in an outbreak disproportionately affecting transgender persons and gay, bisexual, and other men who have sex with men. In 2019, the JYNNEOS vaccine was approved for subcutaneous administration (0.5 ml per dose) to prevent mpox infection. On August 9, 2022, an emergency use authorization was issued for intradermal administration (0.1 ml per dose); however, real-world effectiveness data are limited for either route.
HLA Class II Loss and JAK1/2 Deficiency Coevolve in Melanoma Leading to CD4 T-cell and IFNγ Cross-Resistance
Authors: Simone Stupia, Christina Heeke, Alicia Brüggemann, Anne Zaremba, Beatrice Thier, Julia Kretz, Antje Sucker, Manuel Philip, Gennadiy Zelinskyy, Soldano Ferrone, Alexander Roesch, Susanne Horn, Eva Hadaschik, Dirk Schadendorf, Mirko Trilling, Ulf Dittmer, Klaus Griewank, Fang Zhao, Annette Paschen
Journal: Clinical Cancer Research (2023)

Recent studies have demonstrated HLA class II (HLA-II)-dependent killing of melanoma cells by cytotoxic CD4 T cells. We investigated evolution of HLA-II-loss tumors that escape cytotoxic CD4 T-cell activity and contribute to immunotherapy resistance.Melanoma cells from longitudinal metastases were studied for constitutive and IFN-inducible HLA-II expression, sensitivity towards autologous CD4 T cells, and immune evasion by HLA-II loss. Clinical significance of HLA-II-low tumors was determined by analysis of transcriptomic data sets from patients with immune checkpoint blockade (ICB).Analysis of longitudinal samples revealed strong intermetastatic heterogeneity in melanoma cell-intrinsic HLA-II expression and subclonal HLA-II loss. Tumor cells from early lesions either constitutively expressed HLA-II, sensitizing to cytotoxic CD4 T cells, or induced HLA-II and gained CD4 T-cell sensitivity in the presence of IFNγ. In contrast, late outgrowing subclones displayed a stable CD4 T-cell-resistant HLA-II-loss phenotype. These cells lacked not only constitutive but also IFNγ-inducible HLA-II due to JAK1/2-STAT1 pathway inactivation. Coevolution of JAK1/2 deficiency and HLA-II loss established melanoma cross-resistance to IFNγ and CD4 T cells, as detected in distinct stage IV metastases. In line with their immune-evasive phenotype, HLA-II-low melanomas showed reduced CD4 T-cell infiltrates and correlated with disease progression under ICB.Our study links melanoma resistance to CD4 T cells, IFNγ, and ICB at the level of HLA-II, highlighting the significance of tumor cell-intrinsic HLA-II antigen presentation in disease control and calling for strategies to overcome its downregulation for improvement of patient outcome.
Association of <i>MGMT</i> Promoter Methylation With Survival in Low-grade and Anaplastic Gliomas After Alkylating Chemotherapy
Authors: Connor J. Kinslow, Ann Mercurio, Prashanth Kumar, Ali I. Rae, Markus D. Siegelin, Jack Grinband, Kekoa Taparra, Pavan S. Upadhyayula, Guy M. McKhann, Michael B. Sisti, Jeffrey N. Bruce, Peter D. Canoll, Fabio M. Iwamoto, Lisa A. Kachnic, James B. Yu, Simon K. Cheng, Tony J. C. Wang
Journal: JAMA Oncology (2023)

O6-methylguanine-DNA methyltransferase (MGMT [OMIM 156569]) promoter methylation (mMGMT) is predictive of response to alkylating chemotherapy for glioblastomas and is routinely used to guide treatment decisions. However, the utility of MGMT promoter status for low-grade and anaplastic gliomas remains unclear due to molecular heterogeneity and the lack of sufficiently large data sets.